Process for Preparing Chiral 3-Triazolyl Sulphoxide Derivatives

ABSTRACT

The present invention relates to a catalytic process for preparing 3-triazolyl sulphoxide derivatives in enantiomerically pure or enantiomerically enriched form.

The present invention relates to a catalytic process for preparing3-thiazolyl sulphoxide derivatives in enantiomerically pure orenantiomerically enriched form.

The chemical synthesis of 3-triazolyl sulphoxides is described in theliterature, but leads to a racemic mixture (WO 1999/055668).

Enantiomerically pure chiral sulphoxides and corresponding derivativesare of great significance in the pharmaceutical and agrochemicalindustry. Such compounds can be processed further in order to provideexclusively the biologically active enantiomer of a medicament orchemical crop protection agent. This not only rules out waste in thepreparation process but also avoids potentially harmful side effectswhich can arise from the undesired enantiomer (Nugent et al., Science1993, 259, 479; Noyori et al., CHEMTECH 1992, 22, 360).

Enantioselective synthesis of chiral sulphoxides is described in theliterature. Review articles which describe this methodology can befound, for example, in H. B. Kagan in “Catalytic Asymmetric Synthesis”;I. Ed. VCH: New York 1993, 203-226; Ojirna N. Khiar in Chem. Rev. 2003,103, 3651-3705; K. P. Bryliakov in Current Organic Chemistry 2008, 12,386-404. In addition to the conventionally metal-catalysed methods forsynthesizing chiral sulphoxides, the literature also describes enzymaticand chromatographic processes (K. Kaber in “Biotransformations inOrganic Synthesis”, Springer Ed. 3rd ed. 1997; H. L. Holland, Nat. Prod.Rep., 2001, 18, 171-181). The enzymatic methods are predominantlysubstrate-specific and, moreover, the industrial implementation is verycostly and inconvenient. For example, monooxygenases and peroxidases areimportant enzyme classes which are capable of catalysing a multitude ofsulphides to sulphoxides (S. Colonna et al., Tetrahedron Asymmetry 1993,4, 1981). However, it has been found that the stereochemical result ofthe enzymatic oxidation depends greatly on the sulphide structure.

A frequently employed process for enantioselective oxidation ofthioethers is the Kagan modification to the known method of sharplessepoxidation with chiral titanium complexes (J. Am. Chem. Soc. 1984, 106,8188-8193). This involves “deactivating” the chiral titanium complex,consisting of Ti(OPr^(i))₄ and (+)- or (−)-diethyl tartrate (DET) withone equivalent of water, and catalysing the enantioselective sulphideoxidation of arylalkyl sulphides. However, good results were achievedwith the Kagan reagent with a Ti(OPr^(i))₄/DET/H₂O mixing ratio=1:2:1and an organic peroxide (e.g. tert-butyl hydroperoxide). The goodenantioselectivity of the titanium complexes described is accompanied bya low catalytic activity, which describes the necessary ratio betweensubstrate and catalyst. By means of this process, the direct oxidationof simple arylalkyl sulphides, for example arylmethyl sulphides, tooptically active sulphoxides can be achieved. It has been found that theasymmetric oxidation of, for example, functionalized alkyl sulphidesproceeds with moderate enantioselectivity under these conditions.

Pasini et al. were able to oxidize phenylmethyl sulphide with smallamounts of chiral oxotitanium(IV) Schiff bases and hydrogen peroxide,but with poor enantiomeric excesses (ee-values <20%) (Gaz. Chim. Ital.1986, 116, 35-40). Similar experiences are described by Colona et al.with chiral titanium complexes of N-salicyl-L-amino acids (Org. Bioorg.Chem. 1987, 71-71). In addition, titanium catalysed processes result invery complex workups, which is very disadvantageous for an economicprocess on the industrial scale.

A further method is based on vanadium(IV) Schiff bases as efficientcatalysts for sulphide oxidation. The chiral catalyst is prepared insitu from VO(acac)₂ with a Schiff base of chiral amino alcohols (Synlett1998, 12, 1327-1328; Euro. J. Chem. 2009, 2607-2610). However, thismethod is restricted to simple and nonfluorinated arylalkyl thioethers,for example p-tolylmethyl sulphide.

To date, the enantiomers of 3-triazolyl sulphoxides, which were obtainedin racemic form by literature processes, were obtained by a complexseparation by means of HPLC on chiral phases. The chromatographicseparation of enantiomers or chiral stationary phases is, however,generally unsuitable for relatively large amounts of active ingredient,but serves merely for provision of relatively small amounts.Furthermore, utilization of HPLC on chiral phases is extremely costlyespecially on the preparative scale, owing to the high cost of thesematerials and the considerable investment of time.

There was therefore an urgent need for a catalytic process which isperformable on the industrial scale in particular. It is therefore anobject of the invention to provide such a catalytic process which, inaddition to industrial implementability, ensures inexpensiveness, goodyields and variation of the enantiomer ratio.

In view of the disadvantages and problems outlined above, there is anurgent need for a simplified, industrially and economically performable,catalytic process for enantioselective sulphide oxidation ofsubstituted, fluorinated 3-triazolyl sulphoxide derivatives. The3-triazolyl sulphoxide derivatives obtainable with this desired processshould preferably be obtained with high yield and high purity. Moreparticularly, the process desired should enable the desired targetcompounds to be obtained without the need for complex purificationmethods such as chiral chromatography.

The separation of the enantiomers and also the synthesis of 3-triazolylsulphoxide derivatives which possess a chiral sulphoxide group inenantiomerically pure form or in an enantiomerically enriched form hasnot been described to date

The object was achieved in accordance with the present invention by aprocess for preparing 3-triazolyl sulphoxide derivatives of the generalformula (I),

in whichX¹ and X² are each independently fluorine, chlorine, bromine, hydrogen,(C₁-C₁₂)alkyl, (C₁-C₁₂)haloalkyl,Y¹ and Y² are each independently fluorine, chlorine, bromine, hydrogen,(C₁-C₁₂)alkyl, (C₁-C₁₂)haloalkyl,R¹ and R² are each independently hydrogen, (C₁-C₁₂)alkyl,(C₁-C₁₂)haloalkyl, cyano, halogen, nitro,R³ is hydrogen, (C₁-C₁₂)alkyl, amino, nitro, NH(CO)(C₁-C₁₂)alkyl, N═CR′Rwhere R, R′ are each independently hydrogen, (C₁-C₁₂)alkyl, aryl,characterized in that a sulphide of the formula (II)

in which X¹, X², Y¹, Y², R¹, R² and R³ are each as defined aboveis converted in the presence of a chiral catalyst and of an oxidizingagent.

Preferred, particularly preferred and very particularly preferreddefinitions of the X¹, X², Y¹, Y², R¹, R² and R³ radicals shown in theabovementioned general formula (I) are elucidated hereinafter.

X¹, X², Y¹ and Y² are preferably each independently fluorine, chlorine,hydrogen, (C₁-C₁₂)alkyl, (C₁-C₁₂)haloalkyl,

R¹ and R² are preferably each independently fluorine, chlorine,hydrogen, (C₁-C₁₂)alkyl,

R³ is preferably hydrogen, (C₁-C₁₂)alkyl, amino,

X¹ and X², Y¹ and Y² are more preferably each independently fluorine,chlorine, hydrogen, (C₁-C₁₂)haloalkyl,

R¹ and R² are more preferably each independently fluorine, hydrogen,(C₁-C₆)alkyl,

R³ is more preferably hydrogen, amino,

X¹ and X², Y¹ and Y² are most preferably each independently fluorine,hydrogen, (C₁-C₆)haloalkyl.

R¹ and R² are most preferably each independently fluorine, methyl,

R³ is most preferably hydrogen.

Surprisingly, the chiral 3-triazolyl sulphoxide derivatives of theformula (I) can be prepared under the inventive conditions with goodyields in high purity, which means that the process according to theinvention does not have the disadvantages described in connection withthe prior art.

Compounds of the formula (I) form by the process according to theinvention, according to the preparation conditions, in an enantiomerratio of 50.5:49.5 to 99.5:0.5 (+):(−)-enantiomer or (−):(+)-enantiomer.

The enantiomeric purity can, if necessary, be increased by differentprocesses. Such processes are known to those skilled in the art andinclude especially preferential crystallization from an organic solventor a mixture of organic solvent with water.

The process according to the invention can be illustrated by thefollowing scheme (I):

where X¹, X², Y², R¹, R², R³ are each as defined above.

GENERAL DEFINITIONS

In the context of the present invention, the term “halogens” (Hal),unless defined differently, encompasses those elements which areselected from the group consisting of fluorine, chlorine, bromine andiodine, preference being given to using fluorine, chlorine and bromineand particular preference to using fluorine and chlorine.

Optionally substituted groups may be mono- or polysubstituted, and thesubstituents may be the same or different in the case ofpolysubstitutions.

Alkyl groups substituted by one or more halogen atoms (-Hal) are, forexample, selected from trifluoromethyl (CF₃), difluoromethyl (CHF₂),CF₃CH₂, ClCH₂, CF₃CCl₂.

In the context of the present invention, alkyl groups, unless defineddifferently, are linear, branched or cyclic saturated hydrocarbongroups.

The definition “C₁-C₁₂-alkyl” encompasses the widest range definedherein for an alkyl group. Specifically, this definition encompasses,for example, the meanings of methyl, ethyl, n-, iso-propyl, n-, iso-,sec- and t-butyl, n-pentyl, n-hexyl, 1,3-dimethylbutyl,3,3-dimethylbutyl, n-heptyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl.

In the context of the present invention, aryl groups, unless defineddifferently, are aromatic hydrocarbon groups which may have one, two ormore heteroatoms selected from O, N, P and S.

Specifically, this definition encompasses, for example, the meanings ofcyclopentadienyl, phenyl, cycloheptatrienyl, cyclooctatetraenyl,naphthyl and anthracenyl; 2-furyl, 3-furyl, 2-thienyl, 3-thienyl,2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl,3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-pyrazolyl,4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl,2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl,1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,2,4-thiadiazol-3-yl,1,2,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl, 1,3,4-oxadiazol-2-yl,1,3,4-thiadiazol-2-yl and 1,3,4-triazol-2-yl; 1-pyrrolyl, 1-pyrazolyl,1,2,4-triazol-1-yl, 1-imidazolyl, 1,2,3-triazol-1-yl,1,3,4-triazol-1-yl; 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1,3,5-triazin-2-yl and1,2,4-triazin-3-yl.

In the context of the present invention, unless defined differently,alkylaryl groups are aryl groups which are substituted by alkyl groupsand have an alkylene chain and may have, in the aryl skeleton, one ormore heteroatoms selected from O, N, P and S.

The oxidizing agents which can be used for this reaction are not subjectto any particular stipulations. It is possible to use oxidizing agentswhich are capable of oxidizing corresponding sulphur compounds tosulphoxide compounds. Suitable oxidizing agents for preparing thesulphoxides are, for example, inorganic peroxides, for example hydrogenperoxide, or organic peroxides, for example alkyl hydroperoxides andarylalkyl hydroperoxides. The preferred oxidizing agent is hydrogenperoxide. The molar ratio of oxidizing agent to the sulphide is in therange from 0.9:1 to 4:1, preferably between 1.2:1 and 2.5:1.

The chiral metal-ligand complex is prepared from a chiral ligand and atransition metal compound.

Transition metal derivatives are preferably vanadium derivatives,molybdenum derivatives, zirconium derivatives, iron derivatives,manganese derivatives and titanium derivatives, very preferably vanadiumderivatives. These derivatives can be used, for example, in the form ofthe transition metal(IV) halides, transition metal(IV) alkoxides ortransition metal(IV) acetylacetonates.

The chiral ligand is a chiral compound which is capable, for example, ofreacting with the vanadium derivatives. Such compounds are preferablyselected from chiral alcohols. Preferred chiral ligands likewise includeSchiff bases of the formulae (III) and (IV):

where, in formula (III),R⁴ and R⁵ are each independently hydrogen, (C₁-C₆)alkyl,(C₁-C₆)alkylphenyl, phenyl, halogen, cyano, nitro, cyano(C₁-C₆)alkyl,hydroxy(C₁-C₆)alkyl, (C₁-C₆)alkoxycarbonyl(C₁-C₆)alkyl,(C₁-C₆)alkoxy(C₁-C₆)alkyl,R⁶ is (C₁-C₆)alkyl, halogen-, cyano-, nitro-, amino-, hydroxyl- orphenyl-substituted (C₁-C₆)alkyl, carboxyl, carbonyl(C₁-C₆)alkyl,(C₁-C₆)alkoxycarbonyl(C₁-C₆)alkyl, (C₁-C₆)alkoxy(C₁-C₆)alkyl,(C₁-C₆)alkoxy, di(C₁-C₆)alkoxy(C₁-C₆)alkyl,R⁷ is hydrogen, (C₁-C₆)alkyl, (C₁-C₆)alkylphenyl, aryl,aryl(C₁-C₆)alkyl, preferably tert-butyl, benzyl, phenyl,and chiral carbon atoms are designated *,where, in formula (IV),R⁸ is hydrogen, (C₁-C₆)alkyl, (C₁-C₆)alkylphenyl, phenyl, halogen,cyano, nitro, cyano(C₁-C₆)alkyl, hydroxy(C₁-C₆)alkyl,(C₁-C₆)alkoxycarbonyl(C₁-C₆)alkyl, (C₁-C₆)alkoxy(C₁-C₆)alkyl,R⁹ and R¹⁰ are each hydrogen, (C₁-C₆)alkyl, phenyl, where R⁹ and R¹⁰ mayform a bridge, andchiral carbon atoms are designated *.

These Schiff bases can form a chiral metal-ligand complex, known as achiral (salen)-metal complex. The stoichiometry of the chiral complexesmay vary and is not critical to the invention.

The amount of the chiral metal-ligand complex used, compared to thesulphide, is in the range from 0.001 to 10 mol %, preferably from 0.1 to5 mol %, most preferably 1 to 4 mol %. A higher use of chiralmetal-ligand complex is possible but economically unviable.

The chiral transition metal complex is obtained by reaction of atransition metal derivative and a chiral complex ligand, separately orin the presence of the sulphide.

The conversion of the sulphide of the formula (II) to the compound withthe formula (I) can be performed in the presence of a solvent. Suitablesolvents include in particular: THF, dioxane, diethyl ether, diglyme,methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME), dimethylether (DME), 2-methyl-THF, acetonitrile, butyronitrile, toluene,xylenes, mesitylene, ethyl acetate, isopropyl acetate, alcohols such asmethanol, ethanol, propanol, butanol, ethylene glycol, ethylenecarbonate, propylene carbonate, N,N-dimethylacetamide,N,N-dimethylformamide, N-methylpyrrolidone, halohydrocarbons andaromatic hydrocarbons, especially chlorohydrocarbons such astetrachloroethylene, tetrachloroethane, dichloropropane, methylenechloride, dichlorobutane, chloroform, carbon tetrachloride,trichloroethane, trichloroethylene, pentachloroethane, difluorobenzene,1,2-dichloroethane, chlorobenzene, bromobenzene, dichlorobenzene,chlorotoluene, trichlorobenzene; 4-methoxybenzene, fluorinatedaliphatics and aromatics such as trichlorotrifluoroethane,benzotrifluoride, 4-chlorobenzotrifluoride, and water. It is alsopossible to use solvent mixtures.

It has additionally been observed that the enantiomer ratio can becontrolled not only via the catalyst system but also via the solvent.

Further factors influencing the enantiomer ratio, as well as theoxidizing agent, also include the temperature.

Suitable methods for determining the enantiomeric excess are familiar tothose skilled in the art. Examples include HPLC on chiral stationaryphases and NMR studies with chiral shift reagents.

The reaction is generally performed at a temperature between −80° C. and200° C., preferably between 0° C. and 140° C., most preferably between10° C. and 60° C., and at a pressure up to 100 bar, preferably at apressure between standard pressure and 40 bar.

The preparation of the thioethers of the general formula (II) isdescribed, for example, in WO 1999/055668 or can be performedanalogously.

The ligands are prepared by known processes (Adv. Synth. Catal. 2005,347, 1933-1936).

The desired compounds of the general formula (I) can be isolated, forexample, by subsequent extraction and crystallization.

The present invention is explained in detail by the examples whichfollow, though the examples should not be interpreted in such a manneras to restrict the invention.

Products obtained by the process according to the invention have anenantiomer ratio of 50.5:49.5 to 99.5:0.5, preferably of 60:40 to 95:5,more preferably of 75:25 to 90:10, (+):(−)-enantiomer or(−):(+)-enantiomer, most preferably (+):(−)-enantiomer. Therefore,preference is given in accordance with the invention to those enantiomerratios within the ranges specified which have an excess of the(+)-enantiomer.

The enantiomeric excess may therefore be between 0% ee and 99% ee. Theenantiomeric excess is an indirect measure of the enantiomeric purity ofa compound and reports the proportion of a pure enantiomer in a mixture,the remaining portion of which is the racemate of the compound.

If required, a subsequent crystallization with or without solvent canconsiderably increase the enantiomeric excess. Such processes are knownto those skilled in the art and include especially the preferredcrystallization from an organic solvent or a mixture of organic solventwith water.

PREPARATION EXAMPLES Example 1 Synthesis of(+)-1-{2,4-dimethyl-5-[(2,2,2-trifluoroethyl)sulphinyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-triazole

In a three-neck flask, 10.3 g (27.54 mmol, 95% pure) of1-{2,4-dimethyl-5-[(2,2,2-trifluoroethyl)sulphanyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-triazoleand 145.8 mg (0.55 mmol) of vanadium acetylacetonate were dissolved in36 ml of chloroform and stirred for 10 minutes. Subsequently, 275.8 mg(0.825 mmol) of(S)-(2,4-di-tert-butyl-6-{(E)-[(1-hydroxy-3,3-dimethylbutan-2-yl)imino]methyl}phenolwere added. After 10 minutes, 5.66 g (50 mmol) of 30% H₂O₂ were meteredin over 6 hours. The progress of the conversion was monitored by meansof HPLC. After 4 h of reaction time, a further 145.8 mg (0.55 mmol) ofvanadium acetylacetonate and 275.8 mg of(2,4-di-tert-butyl-6-{(E)-[(1-hydroxy-3,3-dimethylbutan-2-yl)imino]methyl}phenolin 4 ml of chloroform were metered in. Subsequently, 40 ml ofchloroform, 20 ml of water and 20 ml of thiosulphate solution were addedsuccessively. After the aqueous phase had been removed, the organicphase was washed with water and dried over Na₂SO₄, and the solvent wasevaporated under reduced pressure. This gave 10.84 g of grey-browncrystals of(+)-1-{2,4-dimethyl-5-[(2,2,2-trifluoroethyl)sulphinyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-triazole(98% yield, 93.1% HPLC purity) with 2.81% sulphone content. Theenantiomeric excess was determined by means of HPLC on a chiral phase(Daicel Chiracel OJ-RH 150) with a ratio of 16.34:83.66.

The enantiomer ratio was improved, for example by crystallization fromCHCl₃, to 3.39:96.61.

TABLE 1 Oxidation of1-{2,4-dimethyl-5-[(2,2,2-trifluoroethyl)sulphanyl]phenyl}-3-(trifluoro-methyl)-1H-1,2,4-triazole under different conditions:Enantiomer ratio Oxidizing agent Solvent [(−):(+)] H₂O₂ CHCl₃16.34:83.66 H₂O₂ CHCl₃  3.39:96.61 after crystallization from CHCl₃ H₂O₂CHCl₃:toluene 18.54:81.46 tert-Butyl CHCl₃ 50.0:50.0 hydroperoxideCumene CHCl₃ 50:50 hydroperoxide H₂O₂ acetonitrile 50:50 H₂O₂ DME31.49:68.51 H₂O₂ n-butanol 36.61:63.39 H₂O₂ methanol 50:50 H₂O₂ glacialacetic acid 42.58:57.42 H₂O₂ EA 35.18:64.82 H₂O₂ THF 50:50 H₂O₂ Me—THF36.0:64.0 H₂O₂ 4-methoxybenzene 16.33:83.67 1,2-dichlorobenzene18.71:81.29 H₂O₂ chlorobenzene 27.87:72.13 H₂O₂ 4-Cl-benzotrifluoride24.94:75.06 H₂O₂ 1,1,2,2- 18.97:81.03 tetrachloroethane H₂O₂ DMAC46.78:53.22

TABLE 2 Oxidation of1-{2,4-dimethyl-5-[(2,2,2-trifluoroethyl)sulphanyl]phenyl}-3-(trifluoro-methyl)-1H-1,2,4-triazole with different catalysts: Oxidizing Enantiomerratio Catalyst system agent Solvent T [(−):(+)]

H₂O₂ CHCl₃ RT 16.34:83.66

H₂O₂ DCM RT 18.04:81.96

H₂O₂ acetonitrile 40° C. 19.91:80.09

Example 23-(Difluoromethyl)-1-{2,4-dimethyl-5-[(2,2,2-trifluoroethyl)sulphinyl]phenyl}-1H-1,2,4-triazole

Analogously to Example 1,

3-(difluoromethyl)-1-{2,4-dimethyl-5-[(2,2,2-trifluoroethyl)sulphanyl]phenyl}-1H-1,2,4-triazolewas used to obtain3-(difluoromethyl)-1-{2,4-dimethyl-5-[(2,2,2-trifluoroethyl)sulphinyl]phenyl}-1H-1,2,4-triazole.The enantiomeric excess was determined by means of HPLC on a chiralphase (Daicel Chiracel OJ-RH 150) with a ratio of 7.37 92.63.

Example 31-{5-[(2,2-Difluoroethyl)sulphinyl]-2,4-dimethylphenyl}-3-(difluoromethyl)-1H-1,2,4-triazole

Analogously to Example 1,1-{5-[(2,2-difluoroethyl)sulphanyl]-2,4-dimethylphenyl}-3-(difluoro-methyl)-1H-1,2,4-triazolewas used to obtain1-{5-[(2,2-difluoroethyl)sulphinyl]-2,4-dimethylphenyl}-3-(difluoromethyl)-1H-1,2,4-triazole.The enantiomeric excess was determined by means of HPLC on a chiralphase (Daicel Chiracel OJ-RH 150) with a ratio of 19.97:80.03.

1. Process for preparing 3-triazolyl sulphoxide derivatives of theformula (I) in an enantiomerically pure or enantiomerically enrichedform

in which X¹ and X² are each independently fluorine, chlorine, bromine,hydrogen, (C₁-C₁₂)alkyl, (C₁-C₁)haloalkyl, Y¹ and Y² are eachindependently fluorine, chlorine, bromine, hydrogen, (C₁-C₁₂)alkyl,(C₁-C₁₂)haloalkyl, R¹ and R² are each independently hydrogen,(C₁-C₁₂)alkyl, (C₁-C₁₂)haloalkyl, cyano, halogen, nitro, R³ is hydrogen,(C₁-C₁₂)alkyl, amino, nitro, NH(CO)(C₁-C₁₂)alkyl, N═CR′R where R, R′ areeach independently hydrogen, (C₁-C₁₂)alkyl, aryl, characterized in that(A) a sulphide of the formula (II)

in which X¹, X², Y¹, Y², R¹, R² and R³ are each as defined above isconverted in the presence of a chiral catalyst and of an oxidizingagent.
 2. Process according to claim 1, characterized in that theenantiomer ratio is 50.5:49.5 to 99.5:0.5 (+):(−) or (−):(+)-enantiomer.3. Process according to either of claims 1 and 2, characterized in thatthe enantiomer ratio is 50.5:49.5 to 99.5:0.5 (+):(−) enantiomer. 4.Process according to any of claims 1 to 3, characterized in that X¹ andX², Y¹ and Y² are each independently fluorine, chlorine, hydrogen,(C₁-C₁₂)haloalkyl, R¹ and R² are each independently fluorine, hydrogen,(C₁-C₆)alkyl, R³ is hydrogen, amino.
 5. Process according to any ofclaims 1 to 4, characterized in that X¹ and X², Y¹ and Y² are eachindependently fluorine, hydrogen, (C₁-C₆)haloalkyl, R¹ and R² are eachindependently fluorine, methyl, R³ is hydrogen.
 6. Process according toany of claims 1 to 5, characterized in that the oxidizing agents usedare organic or inorganic peroxides.
 7. Process according to any ofclaims 1 to 6, characterized in that the chiral catalyst used is achiral metal-ligand complex, where the metal is a transition metal andthe ligand is a compound of the formula (III) or (IV)

where, in formula (III), R⁴ and R⁵ are each independently hydrogen,(C₁-C₆)alkyl, (C₁-C₆)alkylphenyl, phenyl, halogen, cyano, nitro,cyano(C₁-C₆)alkyl, hydroxy(C₁-C₆)alkyl,(C₁-C₆)alkoxy-carbonykl(C₁-C₆)alkyl, (C₁-C₆)alkoxy(C₁-C₆)alkyl, R⁶ is(C₁-C₆)alkyl, halogen-, cyano-, nitro-, amino-, hydroxyl- orphenyl-substituted (C₁-C₆)alkyl, carboxyl, carbonyl(C₁-C₆)alkyl,(C₁-C₆)alkoxycarbonyl(C₁-C₆)alkyl, (C₁-C₆)alkoxy(C₁-C₆)alkyl,(C₁-C₆)alkoxy, di(C₁-C₆)alkoxy(C₁-C₆)alkyl, R⁷ is hydrogen,(C₁-C₆)alkyl, (C₁-C₆)alkylphenyl, aryl, aryl(C₁-C₆)alkyl, preferablytert-butyl, benzyl, phenyl, and chiral carbon atoms are designated *,where, in formula (IV), R⁸ is hydrogen, (C₁-C₆)alkyl,(C₁-C₆)alkylphenyl, phenyl, halogen, cyano, nitro, cyano(C₁-C₆)alkyl,hydroxy(C₁-C₆)alkyl, (C₁-C₆)alkoxycarbonyl(C₁-C₆)alkyl,(C₁-C₆)alkoxy(C₁-C₆)alkyl, R⁹ and R¹⁰ are each hydrogen, (C₁-C₆)alkyl,phenyl, where R⁹ and R¹⁰ may form a bridge, and chiral carbon atoms aredesignated *.
 8. Process according to any of claims 1 to 7,characterized in that step (A) is followed by performing acrystallization from organic solvent or a mixture of organic solventwith water.
 9. Enantiomerically pure or enantiomerically enriched3-triazolyl sulphoxide derivatives of the formula (I), preparable by theprocess according to any of claims 1 to 8, where the enantiomer ratio is50.5:49.5 to 99.5:0.5 (+):(−)enantiomer.